There are various chemical methods disclosed in the prior art for the synthesis of said cyclic amides also referred as lactams of Formula I.
J. Chem. Soc., Chem. Communication, 1995, 1101-1101 discloses the reaction of hydroxylamine-O-sulfonic acid with alicyclic ketones over SiO2 and no solvent under microwave irradiation to give an amino acid salt, which cyclises in high yield to the corresponding lactam after work up in basic medium.
WO/2009/153470 discloses a method for preparing lactams wherein photonitrosation of a cycloalkane is carried out using nitrosyl chloride (NOCI). According to the invention, said photonitrosation is carried out by means of LEDs emitting a monochromatic light. The method according to the invention also includes a step comprising Beckmann transposition/dechlorination of the oxime hydrochloride generated during said photonitrosation, preferably carried out in a glass micro reactor. The drawback associated with this method is the use of monochromatic light making it difficult to proceed on large scale and therefore limits commercialization of the process.
U.S. Pat. No. 4,054,562 discloses a process for manufacturing a lactam which includes rearranging a cycloalkanone-oxime with sulfuric acid to form the lactam, neutralizing the rearrangement mixture with ammonia to form ammonium sulfate, and separating the lactam and ammonium sulfate. The improvement comprises the recycling of the by-products which are generated during the reaction. However, a major drawback of this process is the high temperatures required, in the range 240°-1250° C. for the decomposition of ammonium sulfate to generate sulfuric acid and its subsequent reuse.
U.S. Pat. No. 2,988,546A discloses a process for the conversion of C10 to C18 cyclic ketones to the corresponding lactams wherein cyclic ketone is reacted with hydrazoic acid in the presence of a strong acid to obtain lactam, the hydrazoic acid being generated from an alkali azide such as sodium azide. The drawback associated with this method is the use of hazardous and unsafe alkali azide.
U.S. Pat. No. 8,309,714B2 discloses a process comprising reaction of cyclododecanone with hydroxylamine in an aqueous solution in the presence of an oxime formation solvent to produce cyclododecanone oxime, b) separating the reaction mixture obtained after the oxime-forming step into an oil and an aqueous phases and collecting a solution of cyclododecanone oxime in the oil phase; (c) removing a part or all of the oxime formation solvent and dissolved water from the solution of cyclododecanone oxime which is collected as an oil phase in the oil/aqueous phase separation step, whereby preparing a solution containing a solvent to be used in a rearrangement reaction in a later step and the cyclododecanone oxime; (d) producing laurolactam from cyclododecanone oxime by rearrangement reaction using an aromatic-ring containing compound as a rearrangement catalyst; and (e) separating and removing the solvent and the rearrangement catalyst from the reaction mixture after the rearrangement step, and purifying the laurolactam. A major drawback of this method is that it involves multiple unit operations as stated herein above.
JP2001019670A, 2001 Jan. 23 discloses a use of a catalyst comprising zeolite-ZnO mixture for rearrangement reaction. The zeolite skeleton is composed of at least silicon, zinc and oxygen and the ratio of Si/Zn in the zeolite skeleton is preferably 10-2,000. The catalyst is obtained by bringing a raw material of silicon oxide, a raw material of zinc oxide and a raw material of an alkali metal into contact with an organic base, such as tetraethylammonium cation, etc., to prepare a mixed solution and maintaining the mixed solution under a specific condition to form the zeolite-ZnO catalyst as a crystal. A Bamberger rearrangement, a Chapman rearrangement, etc., may be cited as the rearrangement reactions using the catalyst besides a Beckmann rearrangement reaction to produce an amide compound from the corresponding oxime compound.
Tetrahedron Letters, 48(40), 7218-7221 (2007) discloses the use of p-toluene sulphonic acid mediated zinc chloride as a very effective catalyst for liquid-phase Beckmann rearrangement of ketoximes in acetonitrile. Reported yield of cyclic amide from corresponding cyclododecanone oxime is 93%.
EP2275407 discloses a process for producing an amide or lactam, wherein catalytic amounts of an acidic chloride, such as thionyl chloride, and a Lewis acid are used in Beckmann rearrangement of an oxime compound. In accordance with the process, side reactions during Beckmann rearrangement can be so controlled that selectivity can be improved and discoloration of the product due to presence of impurities can be minimised, giving a high-quality amide or lactam.
Synthesis, 2002, 1057-1059 discloses solvent free and one step Beckmann rearrangement of ketones and aldehydes by using zinc oxide. It discloses the reaction of ketone or aldehyde with hydroxylamine hydrochloride and ZnO, wherein the reagents were mixed thoroughly and the mixture was heated in an oil bath at 140-170° C. without using any other additional solvent. In case of when cyclohexanone or cycloheptanone reacts with hydroxyl amine hydrochloride in presence of zinc oxide at temperature of 140-170° the reported yields of the corresponding cyclic amides (lactam) are 85% and 83% respectively. In this case the ZnO is used in excess of stoichiometric quantity.
Furthermore, it is known from U.S. Pat. No. 6,649,747 that during the production of laurolactam comprising converting cyclododecanone to an oxime and subjecting the said cyclododecanone oxime to the Beckmann rearrangement reaction, if the temperature of the Beckmann rearrangement reaction is too high, the cyclododecanone oxime gets decomposed, and the resultant laurolactam is unsatisfactory due to the low quality thereof
Therefore, it is seen that the technical problem associated with the prior art include,                1. Use of multiple solvents and isolation/purification at intermediate stages, thereby increasing the unit operations and resulting into the reduced yield and increased cost of the process.        2. Decomposition of oxime at high temperature.        3. Formation of impurities during the Beckmann rearrangement reaction due to high temperature and high acidity, resulting in low yields.        4. Discoloration of the product due to impurity formation during the Beckmann rearrangement stage.        
The processes disclosed in the prior art and described hereinabove suffer from various drawbacks such as need for multiple unit operations like solvent recovery and/or isolation/purification at intermediate stage, lower yield and poor quality of product, or are otherwise unsuitable for large-scale industrial production. This necessitates the development of an improved process for the preparation of cyclic amides of Formula I, also referred to as lactams, which minimizes the use of solvents and the number of unit operations, provides better yield and higher purity of product and is suitable for large-scale industrial scale manufacture.
Although the method reported in Synthesis, 2002, 1057-1059 discloses solvent free and one step Beckmann rearrangement of ketones and aldehydes by using zinc oxide, it has been found that lactam formed undergoes the polymerization resulting into low yield and low purity with polymer as an impurity.
The inventors of the present invention based on their expertise and experiments revealed that when hydroxylammonium salt reacts with the amphoteric metal oxide or amphoteric masked metal oxide to produce the corresponding metal salt, the presence of metal salt in excess can reduce the purity and yield of the final product in the subsequent rearrangement reaction, as understood from the example illustrated herein below.
For example, when zinc oxide reacts with hydroxyl amine hydrochloride, it produces water and zinc chloride.2NH2OH.HCl+ZnO→2NH2OH+ZnCl2+H2O
It has been observed by the inventors of the present invention that excess amount of ZnCl2 causes the polymerization of the lactam so produced during the reaction at later stage. Therefore, it is essential to control the amount of metal salt present in the reaction medium to avoid polymerization of said lactam and isolate high purity cyclic lactam in high yield.
The inventors of the present invention have addressed the issue by providing a solution comprising use of a base in combination with the amphoteric metal oxide or amphoteric masked metal oxide, which results in increased yield and the purity of the cyclic amide formed.
There has not been any teaching or motivation in the prior art which can address the shortcomings in the prior art for preparing cyclic amides of Formula I comprising using amphoteric metal oxide or amphoteric masked metal oxide in combination with a base for the formation of corresponding oxime, and which after oxime formation provides a suitable reaction medium with desired level of corresponding metal salt for facilitating the subsequent in-situ rearrangement into corresponding lactam, without causing excess polymerization, comprising the use of amphoteric metal oxide or amphoteric masked metal oxide in less than stoichiometric quantities, the use of base to neutralize the remaining acid, and optionally leaving a small quantity of free acid to catalyze the subsequent reaction, whereby corresponding lactam is obtained in substantially high yield, and free of polymer impurity.
While working on the development of the present invention, the inventors observed that when cyclic ketone reacts with hydroxyl amine hydrochloride in presence of amphoteric metal oxide or amphoteric masked metal oxide in stoichiometric quantity it yielded only 61% of corresponding cyclic amide (w/w on cyclic ketone).
It was found that when the amphoteric metal oxide or amphoteric masked metal oxide was used in combination with a base, the yield of cyclic amide is significantly increased.
Furthermore, it was found that when the quantity of amphoteric metal oxide or amphoteric masked metal oxide in combination with base used resulted in complete neutralization of the acid component of the hydroxylammonium salt, the subsequent rearrangement reaction was sluggish, and that the presence of some acidity was required to facilitate the subsequent rearrangement reaction.
Furthermore, it was found that the required acidity is achieved by adjusting the quantity of amphoteric metal oxide or amphoteric masked metal oxide in combination with base used in the preparation of oxime to less than stoichiometric quantity required for complete neutralization of the acid component of the hydroxylammonium salt. Alternatively acidic material such as p-toluene sulfonic acid, is separately introduced after the oxime preparation to facilitate the subsequent rearrangement.
Furthermore, when no amphoteric metal oxide or amphoteric masked metal oxide is used and the reaction of cyclic ketone and hydroxyl amine salt is allowed to take place in presence of a base only, the obtained yield of corresponding amide was low, substantiating the observation of the inventors that it is advantageous to use the combination of amphoteric metal oxide or amphoteric masked metal oxide and a base in a suitable ratio to obtain high purity lactam in high yield and without formation of polymer.
The results are illustrated herein below in Table 1, for the preparation of laurolactam wherein zinc oxide represents the amphoteric metal oxide or amphoteric masked metal oxide and sodium carbonate represents the base.
TABLE 1CyclododecanoneNH2OH•HClZnONa2CO3laurolactam YieldCondition(mol)(mol)(mol)(mol)(w/w cyclododecanone)Only ZnO1.01.1—0.5 61%used inreactionCombination1.01.1 0.050.4563.7%of ZnO and(additional ZnCl2 wasNa2CO3 usedadded in second stagein reactionto complete reaction)1.01.10.10.496.11.01.10.20.387.9%Only Na2CO31.01.1—0.5 34%used in thereaction
The present invention discloses a straight through process for manufacture of cyclic amides, also called as lactams, and provides an excellent process providing solution to the problems associated with the processes disclosed therein in the prior art for the preparation of cyclic amides of Formula I and the details are described herein after in the description.
The object of the present invention is to provide a solution to the technical problems associated with the processes disclosed therein the prior art for the preparation of cyclic amides of Formula I also referred as lactams. Keeping the said objective in view, the present invention provides an industrially viable and economical process thereby eliminating the above mentioned shortcomings associated with the processes disclosed in the prior art for the preparation of cyclic amides of Formula I.